[unreadable] [unreadable] Ozone (O3) is the principle oxidative air pollutant in most American cities. This program has established that the pathobiologic response of mammalian respiration to inhalation of ambient concentrations of O3 centers on the epithelium and varies by species, position within the airway tree and duration of exposure. The focus of this proposal is the cellular, physiologic, and molecular mechanisms by which exposure to oxidant air pollutants, in concert with allergens, contributes to the development of asthma. The overall hypothesis being tested is that the episodic nature of environmental exposure to oxidant air pollutants: a) promotes the development of asthma and exacerbates the allergen response in asthmatics by altering the homeostasis of the airway epithelial-mesenchymal trophic unit in adults; and b) elevates the severity of asthma in the young by fundamentally altering the postnatal development of these trophic interactions. These changes result from continual cycles of acute injury, inflammation and repair superimposed on the immune response to allergen exposure. This supplement will address changes in the nervous components of the epithelial-mesenchymal trophic unit through two specific aims: 1) structure and function of the airway parasympathetic neural component in developing neonatal and young rhesus monkeys and 2) the neuroplasticity of these parasympathetic neurons during airway hyperresponsiveness. Together with the three principal projects, this proposal will also compare responses in the same neonatal and adult rhesus monkeys following episodic exposure to O3 and repeated challenge with a human allergen, house dust mite, during either the injury/inflammation phase of O3 exposure or the repair phase. [unreadable] [unreadable] [unreadable]